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Tricyclic antidepressants (TCA) are among the oldest antidepressants that are also indicated for the treatment of various pain conditions. This drug class includes cationic amphiphilic molecules characterized by a positively charged hydrophilic head group. Microgels consist of cross-linked polymers and can act as drug delivery systems that protect drugs from degradation, as well as release drugs when exposed to high ionic strength. Studying these drug-microgel interactions using microfluidics is beneficial as it reduces product drop and costs. Therefore, the aim of this study is to investigate with a microfluidics-based method how the microgels (Hyaluronic acid (HA), Polyacrylate (PA) and DC beads) with a scale of 100-300 mm in diameter interact with the amphiphilic antidepressant drugs (Amitriptyline (AMT), Doxepin (DOX) and Chlorpromazine (CPZ)), as well as investigating whether the aforementioned gels could function as drug formulations. The experiments were divided into two studies binding and release studies. Binding studies were done for different concentrations of AMT, DOX and CPZ. Binding studies of AMT, DOX and CPZ to PA gels, HA gels and DC beads only took place in phosphate buffer. For amphiphilic drugs, a Critical Association Concentration (CAC) and Critical collapse concentration (CCC) were first determined where the kinetics of binding and release were carefully studied. This work's results showed similarities and differences between AMT, CPZ, and DOX interacting with DC, PA, and HA gels by using microfluidics-based method. Lower concentration of substance caused less electrostatic interactions between drug and the microgels, leading to less shrinkage of microgels. The higher the net charge of a drug, the more electrostatic interactions with microgels, resulting in slower release. Therefore, microgel volume change is time-dependent for both binding and release. The ion-binding property of microgels is particularly useful in drug delivery, where linear and cross-linked former of the negatively charged polymer can act as carriers of cationic self-assembled drugs, it tells us that microgels can be used as drug formulations.